Abstract 3816
Background
Radium-223 dichloride (Ra-223) is a targeted alpha-emitter that selectively binds to areas of increased bone turnover in bone metastases. In the ALSYMPCA trial an increased overall survival over placebo in both docetaxel pretreated (14.4 mo) and docetaxel untreated (16.1 mo) patients was shown. With multiple life-prolonging agents (LPD), data on treatment sequencing and outcomes in real-world practice are needed. The aim of this study was to investigate the use of Ra-223 and outcomes in daily practice in the Netherlands.
Methods
Patients treated with Ra-223 in the CAPRI registry were included and followed until 01-01-2018. Subgroups were based on prior use of docetaxel (docetaxel naive, DOC-naïve; post-docetaxel, post-DOC). Outcomes were treatment sequence and overall survival from 1st Ra-223 injection.
Results
288 patients treated with Ra-223 were included in this analysis. 90% were pretreated with one or more lines of LPD (38% 1 line, 52% ≥1 line). 33% of DOC-naïve patients were treated with Ra-223 as line 1. Baseline characteristics are shown in the table. DOC-naïve patients had prognostic favorable baseline characteristics compared to post-DOC patients, namely higher hemoglobin (7.9 vs 7.4 mmol/L, p < 0.01), lower PSA (85 vs 147 µg/L, p < 0.01) and longer period from castration to mCRPC (16.8 vs 13.1 months, p < 0.01). 47% completed all 6 cycles. 43% were alive or lost-to-follow-up at database cutoff. Median overall survival was 12.2 months (IQR 7-24 months), with longer median overall survival in DOC-naïve compared to post-DOC patients (17.0 vs 11.2 months, p < 0.01).Table:
869P
Radium-223 N = 288 | Doc-naïve N = 120 | Post-doc N = 168 | p-value | |
---|---|---|---|---|
Age ≥75 years (%) | 46 | 63 | 33 | <0.01 |
Extent of disease (%) N0 / N1 / Nx M0 / M1 / Mx (visceral) | 54 / 20 / 26 71 / 4 / 26 | 57 / 23 / 21 76 / 3 / 21 | 52 / 18 / 30 67 / 4 / 29 | 0.62 0.78 |
Charlson score (%) 6 7-8 9-10 >10 | 64 30 6 1 | 64 30 5 1 | 63 30 6 1 | 0.98 |
ECOG (%) 0 1 >1 Missing | 19 48 13 20 | 24 43 13 19 | 16 51 13 20 | 0.21 |
Hb, mmol/L Median (IQR) Missing (%) | 7.7 (6.8-8.3) 10 | 7.9 (7.1-8.4) 10 | 7.4 (6.6-8.1) 10 | <0.01 |
LDH, U/L Median (IQR) Missing (%) | 243 (201-310) 33 | 240 (205-288) 31 | 248 (197-332) 34 | 0.60 |
ALP, U/L Median (IQR) Missing (%) | 153 (91-267) 14 | 139 (87-227) 14 | 167 (94-274) 14 | 0.11 |
PSA, µg/L Median (IQR) Missing (%) | 124 (48-344) 13 | 85 (44-205) 14 | 147 (55-444) 13 | <0.01 |
Period from castration to mCRPC, months Median (IQR) | 14.3 (8-27) | 16.8 (9-28) | 13.1 (8-23) | <0.01 |
Previous ART use, % Yes No | 80 20 | 76 24 | 83 17 | 0.12 |
ART, androgen-receptor targeting drugs (i.e. abiraterone acetate or enzalutamide)
Conclusions
Although Ra-223 was positioned as a later line of mCRPC in this Dutch real-world practice than in the ALSYMPCA trial, overall survival was comparable. This is probably explained by adequate patient selection. Further research on the best timing of Ra-223 in the treatment of mCRPC is awaited.
Clinical trial identification
NL3440 (NTR3591).
Editorial acknowledgement
Legal entity responsible for the study
Institute for Medical Technology Assessment, Erasmus University Rotterdam.
Funding
Sanofi-Aventis Netherlands B.V., Janssen-Cilag B.V., Astellas Pharma B.V., and Bayer B.V.
Disclosure
M.C.P. Kuppen: Travel / Accommodation / Expenses: Ipsen. H.M. Westgeest: Travel / Accommodation / Expenses: Ipsen; Honoraria (self): Roche. A.J.M. van den Eertwegh: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Oncology; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Merck. J. Van Moorselaar: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Sanofi-Genzyme. N. Mehra: Research grant / Funding (institution): Astellas; Honoraria (self), Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Sanofi; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self): Merck; Honoraria (self): Bayer; Honoraria (self): BMS; Honoraria (self): MSD. J.L. Coenen: Advisory / Consultancy: Sanofi. I. van Oort: Advisory / Consultancy, Research grant / Funding (self): Astellas; Advisory / Consultancy, Research grant / Funding (self): Janssen; Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy: Roche; Advisory / Consultancy: Mdx health. D.M. Somford: Research grant / Funding (institution): Astellas. R. de Wit: Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Advisory / Consultancy: Merck Sharp Dohme; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Janssen; Advisory / Consultancy: Clovis. A.M. Bergman: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Speaker Bureau / Expert testimony: Janssen. C. Uyl-de Groot: Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Janssen-Cilag; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Genzyme; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Glycostem Therapeutics; Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca. W.R. Gerritsen: Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Bavarian Nordic; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen-Cilag; Advisory / Consultancy: Amgen; Advisory / Consultancy: CureVac; Advisory / Consultancy: Dendreon; Advisory / Consultancy: Merck (MSD); Advisory / Consultancy: Morphosys; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Aglaia Biomedical Ventures; Advisory / Consultancy: PsiOxus Therapeutics. All other authors have declared no conflicts of interest.
Resources from the same session
3252 - Genes involved in DNA replication, chromatin remodeling and cell cycle as potential biomarkers for therapy outcome to immune therapy in patients with metastatic cutaneous malignant melanoma
Presenter: Fernanda Costa Svedman
Session: Poster Display session 3
Resources:
Abstract
5545 - Phase Ib/II Study (SENSITIZE) assessing safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical outcome of domatinostat in combination with pembrolizumab in patients with advanced melanoma refractory/non-responding to prior checkpoint inhibitor therapy
Presenter: Jessica Hassel
Session: Poster Display session 3
Resources:
Abstract
5213 - Genomic landscape of primary malignant melanoma of esophagus
Presenter: Jie Dai
Session: Poster Display session 3
Resources:
Abstract
2716 - A phase III, randomised, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation in patients with high-risk cutaneous squamous cell carcinoma (CSCC)
Presenter: Danny Rischin
Session: Poster Display session 3
Resources:
Abstract
3550 - ILLUMINATE 301: A randomized phase 3 study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy
Presenter: Marcus Butler
Session: Poster Display session 3
Resources:
Abstract
1645 - PRIME002 - Early phase II study of Azacitidine and Carboplatin priming for Avelumab in patients with advanced melanoma who are resistant to immunotherapy
Presenter: Andre Van Der Westhuizen
Session: Poster Display session 3
Resources:
Abstract
4440 - Pembrolizumab (pembro) Plus Lenvatinib (len) for First-Line Treatment of patients (pts) With Advanced Melanoma: Phase 3 LEAP-003 Study
Presenter: Alexander Eggermont
Session: Poster Display session 3
Resources:
Abstract
3454 - Proof of concept study with the histone deacetylase inhibitor vorinostat in patients with resistant BRAFV600 mutated advanced melanoma
Presenter: Sanne Huijberts
Session: Poster Display session 3
Resources:
Abstract
1832 - A phase Ia/Ib clinical study to evaluate the safety, pharmacokinetics (PK) and preliminary anti-tumor activity of FCN-159 in patients with advanced melanoma harboring NRAS-aberrant (Ia) and NRAS-mutation (Ib).
Presenter: Lu Si
Session: Poster Display session 3
Resources:
Abstract
3996 - A Phase I Clinical Trial Investigating the Therapeutic Cancer Vaccine UV1 in Combination with Pembrolizumab as First-Line Treatment of Patients with Malignant Melanoma
Presenter: Sanjiv Agarwala
Session: Poster Display session 3
Resources:
Abstract